The invention concerns a dialysis membrane for hemodialysis in the form of flat foils, tube foils or hollow filaments of regenerated cellulose.
Dialysis membranes of regenerated cellulose for hemodialysis, in the form of flat foils, tube foils or hollow filaments have been known for a long time, and are employed as before preferably in artificial kidneys, although many characteristics causing difficulties can still not be eliminated.
Thus a dialysis membrane for hemodialysis is known from DE-PS 27 05 735, with decreased thrombogenic activity of cellulose with chemically bound antithrombogenic compounds therein, whereby the dialysis membrane is composed of two or more layers of a cellulose regenerated from cuoxam cellulose solutions, which have each been obtained from separately fed slits of a spinning nozzle, whereby the cellulose layer disposed on the blood side is completely or partially of a modified cellulose which contains the antithrombogenic active substance chemically bound therein.
It has, however, already been suggested in DE OS 17 20 087 that the polymer material of the membrane be reacted with an alkyl halogenide and thereafter the obtained material be reacted with an alkali salt of an antithrombogenic compound with cationic group (e.g., heparin or a heparinoid compound) in order to decrease the danger of coagulation of the blood. Therewith also halogen alkyl dialkylamine have been ranked among the possible alkyl halogenides. Also cellulose, however, substantially cellulose acetate, numbers among the possible polymers.
Aside from the fact that dialysis membranes of synthetic or natural polymers can very easily cause a coagulation of the blood upon their employment in artificial kidneys, which is extensively prevented by means of appropriate treatment with medicaments or by means of the above-described particular dialysis membranes, there frequently occurs a further problem with dialysis membranes of regenerated cellulose, which previously could still not be satisfactorily solved, and indeed it has been established that with the treatment of a sick kidney with dialyzators with cellulose membranes a temporary leukocyte decrease can occur in the first period of the dialysis treatment. This effect is designated as leukopenia.
Leukopenia is a lowering of the leukocyte number (white blood cells) in the blood circulation. The number of white blood cells in humans amounts to about 4,000 up to about 12,000 cells/mm.sup.3.
The leukopenia upon dialysis is most strongly pronounced 15/20 minutes after the start, whereby the neutrophiles (i.e., the leukocytes which are colorable with neutral or simultaneously with acid and basic dyes) can almost completely disappear. Thereafter, the number of leukocytes recovers within about one hour again to nearly the starting value, or exceeds this.
If after recover of the leukocytes a new dialyzator is connected, leukopenia occurs again to the same extent.
Cellulose membranes cause a pronounced leukopenia. Even if the clinical significance of the leukopenia is not scientifically clarified, there exists still a desire for a dialysis membrane for hemodialysis which does not display the effects of leukopenia, without thereby impairing the other very desirable characteristics of dialysis membranes of regenerated cellulose.
Surprisingly it has been discovered that a dialysis membrane of regenerated cellulose characterized in that at least at one membrane surface, bridge-forming polymeric acids are chemically bound to the cellulose, display a clearly decreased leukopenia, so that the number of leukocytes falls only to about 80% of the starting value, whereas with unaltered regenerated cellulose the number of leukocytes has fallen to about 20% of the starting value after about 15 minutes of dialysis time.
From DE OS 31 36 573 is known the production of a dialysis membrane of regenerated cellulose, for which production a liquid mass is employed which contains a reaction product of a copper ammonium cellulose with an ammonium- or alkali-metal salt of a polymerizate with 10 to 70 equivalent percent carboxyl groups and an average molecular weight number in the range from 500 up to 200,000, and a membrane is manufactured by means of shaping the particular mass into a dome- or foil-like shape, immersing the obtained shape in dilute sulfuric acid solution for its coagulation and regeneration, and subsequently, immersing the shape into a strongly basic solution for washing out the ammonium- or alkali-metal salt of the polymerizate (from the shaped body) and formation of fine pores (in the shaped body) corresponding substantially to the molecular weight of the salt.